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Results for “PROLIFERATION”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 559 records · Page 31
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

EVA1A inhibits GBM cell proliferation by inducing autophagy and apoptosis

Eva-1 homolog A (EVA1A) is a novel lysosome and endoplasmic reticulum-associated protein involved in autophagy and apoptosis. In this study, we constructed a recombinant adenovirus 5-EVA1A vector (Ad5-EVA1A) to overexpress EVA1A in glioblastoma (GBM) cell lines and evaluated its anti-tumor activities in vitro and in vivo. We found that overexpression of EVA1A in three GBM cell lines (U251, U87 and SHG44) resulted in a suppression of tumor cell growth via activation of autophagy and induction of cell apoptosis in a dose- and time-dependent manner. EVA1A-mediated autophagy was associated with inactivation of the mTOR/RPS6KB1 signaling pathway. Furthermore in vivo, overexpression of EVA1A successfully inhibited tumor growth in NOD/SCID mice. Our data suggest that EVA1A-induced autophagy and apoptosis play a role in suppressing the development of GBM and their up-regulation may be an effective method for treating this form of cancer. - Highlights: • Overexpression of EVA1A suppresses GBM cell growth. • EVA1A induces autophagy through the mTOR/RPS6KB1 pathway. • EVA1A induces GBM cell apoptosis. • EVA1A inhibits the development of GBM in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Sorafenib derivatives-functionalized gold nanoparticles confer protection against tumor angiogenesis and proliferation via suppression of EGFR and VEGFR-2

Sorafenib is a multi-kinase inhibitor that has been highlighted as a tumor suppressor due to its anti-proliferative and anti-angiogenic properties, whereas the clinical application of Sorafenib is restricted by the side effects it may cause. The past decade has witnessed the development of a series of sorafenib derivatives to improve the clinical performance of sorafenib. Gold nanoparticles (AuNPs) have been widely utilized in drug delivery systems due to their unique properties, including biocompatible nature, simple preparation, and easy surface modification. Herein, this study is aimed to investigate the anti-tumor effects of new sorafenib derivatives-capped gold nanoparticles (AuNPs-New Sor) in tumor formation and metastasis as well as the underlying mechanisms. Initially, new sorafenib derivatives were constructed and combined with AuNPs to form AuNPs-New Sor, and the properties of synthesized AuNPs-New Sor were identified in a mouse model of tumorigenesis. The effect of AuNPs-New Sor on tumor vascular normalization was investigated by assessing vascular permeability and perfusion rate. Next, we evaluated the effect of AuNPs-New Sor on migration and viability of tumor cells and human umbilical vein endothelial cells (HUVECs) as well as on HUVEC angiogenesis in vitro. A melanoma mouse model was further established for in vivo substantiation of the anti-tumor effect of AuNPs-New Sor. According to the results, AuNPs could deliver new sorafenib derivatives into tumor tissues and downregulate the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2), thereby suppressing tumor migration, EMT, and angiogenesis in vitro. In addition, AuNPs-New Sor displayed competitive anti-tumor activities in vivo. Taken together, AuNPs-New Sor may attenuate tumor development and angiogenesis through downregulation of EGFR and VEGFR-2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Path Toward a Breeding, Proliferation-Resistant, Thermal-Spectrum Molten Salt Reactor

Liquid-fueled, thermal-spectrum molten salt breeder reactors (TS-MSBRs) offer the potential for affordable, safe, inexhaustible energy with minimal potential for nuclear material misuse and without significant actinide waste generation. Realizing the full set of TS-MSBR capabilities is only now becoming possible with the advent of advanced fuel-salt processing techniques, improved materials, and a more detailed understanding of fuel-salt properties. Additionally, modern higher-fidelity modeling and simulation methods enable a more detailed evaluation of TS-MSBR design options. TS-MSBRs, however, remain immature and will require substantial, sustained development resources.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2019

Mitigating the Threat of Nuclear-Weapon Proliferation via Nuclear-Submarine Programs

Brazil is building a nuclear-powered attack submarine, South Korea has in the past asserted its need for nuclear-powered attack submarines to deal with the threat of North Korean nuclear-armed submarine-launched ballistic missiles, and Iran has asserted more vaguely its need for naval nuclear propulsion. All three countries are non-weapon-state parties to the Nuclear Nonproliferation Treaty (NPT). Their interest in naval reactors brings with it two challenges to the NPT: 1) The safeguards “loophole” under which a country can withdraw nuclear materials from IAEA safeguards indefinitely for allowed “non-peaceful activities;” and 2) A justification for the acquisition of national uranium-enrichment facilities because the international suppliers of enrichment services have peaceful-use requirements. In fact, Brazil’s acquisition of enrichment was driven by its navy. It is argued, however, that nuclear-powered attack submarines have advantages over modern conventional attack submarines primarily in their ability to transit great distances at high speed whereas only a few countries have foreign military commitments requiring such capabilities. For defense of nearby waters against foreign navies, attack submarines are merely one component of a complex system of anti-submarine aircraft and surface vessels and underwater sensor networks. Conventional attack submarines are no less effective and much less costly than nuclear-powered attack submarines in this role.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗
DOE OSTI2015

Optimized Sampling Strategies For Non-Proliferation Monitoring: Report

Concentration data collected from the 2013 H-Canyon effluent reprocessing experiment were reanalyzed to improve the source term estimate. When errors in the model-predicted wind speed and direction were removed, the source term uncertainty was reduced to 30% of the mean. This explained the factor of 30 difference between the source term size derived from data at 5 km and 10 km downwind in terms of the time history of dissolution. The results show a path forward to develop a sampling strategy for quantitative source term calculation.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2020

Event Definition for the Automated Detection of Nuclear Proliferation Activities

In FY2020, Savannah River National Laboratory (SRNL) in collaboration with the Discovery Analytics Center (DAC) at Virginia Polytechnic Institute and State University (VT) began developing a demonstration prototype system that uses multiple machine learning and data analytic methods on largescale open data sources to identify new, developing, or undeclared nuclear programs. One of the most challenging aspects of applying machine learning techniques to such a problem is the high likelihood of extremely sparse data from disparate sources. To overcome this challenge, the current work will use a strategic combination of supervised, semi-supervised, and unsupervised learning techniques to ingest and fuse data streams to make a forecast of nuclear activities in a targeted geospatial location. Identifying potential data sources and training supervised learning algorithms is dependent upon the development of a robust foundation of targeted event domains that fundamentally define the nuclear activities of interest. This report documents the definition of a hierarchical structure for both nuclear activity and event domains that will be used to guide the research team in development or use of existing semantic dictionaries that are instrumental to searching, parsing, and categorizing events for the forecasting system’s use.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Machine Learning Using Open Data Sources for Detection of Nuclear Proliferation Activities (U)

In FY2020, Savannah River National Laboratory (SRNL) in collaboration with the Sanghani Center for Artificial Intelligence and Data Analytics (SCAIDA) at Virginia Polytechnic Institute and State University (VT) and funded by the Department of Energy’s (DOE) Defense Nuclear Nonproliferation Research and Development, began developing a demonstration prototype system that uses multiple machine learning and data analytic methods on large-scale open data sources to identify new, developing, and/or undeclared nuclear programs. Using the announcement in May 2018 of the proposed Savannah River Plutonium Processing Facility (SRPPF) as a test subject, the goal of this 2-year project is to forecast the SRPPF using only data prior to May 2018. The project work is split into a preliminary prototype development for the first year with an initial evaluation of viability followed by the second year of development to create an integrated prototype system and more extensive performance evaluation. This report documents the results of the preliminary-phase tasks.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗
DOE OSTI2016

ADP‐Induced Ca 2+ Signaling and Proliferation of Rat Ventricular Myofibroblasts Depend on Phospholipase C‐Linked TRP Channels Activation Within Lipid Rafts

Nucleotides released during heart injury affect myocardium electrophysiology and remodeling through P2 purinoceptors activation in cardiac myofibroblasts. ATP and UTP endorse [Ca 2+ ] i accumulation and growth of DDR‐2/α‐SMA‐expressing myofibroblasts from adult rat ventricles via P2Y 4 and P2Y 2 receptors activation, respectively. Ventricular myofibroblasts also express ADP‐sensitive P2Y 1 , P2Y 12 , and P2Y 13 receptors as demonstrated by immunofluorescence confocal microscopy and western blot analysis, but little information exists on ADP effects in these cells. ADP (0.003–3 mM) and its stable analogue, ADPßS (100 μM), caused fast [Ca 2+ ] i transients originated from thapsigargin‐sensitive internal stores, which partially declined to a plateau sustained by capacitative Ca 2+ entry through transient receptor potential (TRP) channels inhibited by 2‐APB (50 μM) and flufenamic acid (100 μM). Hydrophobic interactions between G q/11 ‐coupled P2Y purinoceptors and TRP channels were suggested by prevention of the ADP‐induced [Ca 2+ ] i plateau following PIP 2 depletion with LiCl (10 mM) and cholesterol removal from lipid rafts with methyl‐ß‐cyclodextrin (2 mM). ADP [Ca 2+ ] i transients were insensitive to P2Y 1 , P2Y 12 , and P2Y 13 receptor antagonists, MRS2179 (10μM), AR‐C66096 (0.1 μM), and MRS2211 (10μM), respectively, but were attenuated by suramin and reactive blue‐2 (100 μM) which also blocked P2Y 4 receptors activation by UTP. Cardiac myofibroblasts growth and type I collagen production were favored upon activation of MRS2179‐sensitive P2Y 1 receptors with ADP or ADPßS (30 μM). In conclusion, ADP exerts a dual role on ventricular myofibroblasts: [Ca 2+ ] i transients are mediated by fast‐desensitizing P2Y 4 receptors, whereas the pro‐fibrotic effect of ADP involves the P2Y 1 receptor activation. Data also show that ADP‐induced capacitative Ca 2+ influx depends on phospholipase C‐linked TRP channels opening in lipid raft microdomains. J. Cell. Physiol. 232: 1511–1526, 2017. © 2016 Wiley Periodicals, Inc.

Certal, Mariana↗
DOE OSTI2019

Semaphorin 3A Negatively Affects Proliferation of Mouse Thymus Epithelial Cells In Vitro

We studied effects of semaphorin 3A, keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and their combinations on the proliferative activity of cortical (cTEC1-2) and medullary (mTEC3-10) thymus epithelium cell lines. Semaphorin 3A inhibited the proliferative activity of epithelial cells, while HGF and KGF, in contrast, exerted a stimulating effect. The effect of KGF and semaphorin 3A on different cell lines depended on the expression of receptors for these two factors. When the combination of two factors was used, semaphorin 3A was able to neutralize the stimulating effect of HGF and KGF. It can be assumed that semaphorin 3A synthesized in the thymus stroma, can act as a functional antagonist of HGF and KGF and have an inhibitory effect when these drugs are administered into the body for the therapeutic purpose of restoring thymus functions.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Identification of important invasion and proliferation related genes in adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is an end‐stage hormonal syndrome. Although profound attempts have been made to illuminate the pathogenesis, the molecular mechanisms of ACC remain to be clarified. To identify the important genes in the progression of ACC, microarray datasets GSE19775 was downloaded from the gene expression omnibus database. The differentially-expressed genes (DEGs) were identified, and pathway and GO enrichment analyses were performed. The protein–protein interaction (PPI) network was constructed and the module analysis was performed using the protein interaction network analysis and Cytoscape. Also constructed target genes–miRNA regulatory network and target genes–TF regulatory network. Correlation of the hub genes were analyzed in The Cancer Genome Atlas. The prognostic values of hub genes were further validated by online tool UALCAN. Mutation analysis was done by online tool CBio Cancer Genomics Portal. A total of 884 DEGs were identified, with 441 in up regulation and 443 in down regulation. Pathways in catecholamine biosynthesis, aldosterone synthesis and secretion, pyrimidine deoxyribonucleosides salvage and systemic lupus erythematosus were the most significantly enriched for DEGs (up and down regulated). Blood vessel morphogenesis and cell cycle phase transition were the most significantly enriched term in biological processes, while extracellular matrix and chromosome, centromeric region were in cellular component and heparin binding and protein dimerization activity were in molecular function. Among the PPI networks and its module, target genes–miRNA regulatory network and target genes–TF regulatory network, hub genes were YWHAZ, FN1, GRK5, VCAM1, GATA6, TXNIP, HSPA1A, and F11R. Hub genes such as YWHAZ, STAT1, ICAM1, SH3BP5, CD83, FN1, TK1, HIST1H1C, CABLES1, and MCM3 were associated with poor overall survival, while hub genes such as STAT1, ICAM1, CD83, FN1, TK1, HIST1H1C, and MCM3 were highly expressed in stage 4. In conclusion, DEGs and hub genes diagnosed in this study may deepen our understanding of molecular mechanisms underlying the progression of ACC, and provide important targets for diagnosis and treatment of ACC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

CD27{sup -}CD45{sup +} γδ T cells can be divided into two populations, CD27{sup -}CD45{sup int} and CD27{sup -}CD45{sup hi} with little proliferation potential

In addition to the majority of T cells which carry the αβ T cell receptor (TCR) for antigen, a distinct subset of about 1–5% of human peripheral blood T cells expressing the γδ TCR contributes to immune responses to infection, tissue damage and cancer. T cells with the Vδ2{sup +} TCR, usually paired with Vγ9, constitute the majority of these γδ T cells. Analogous to αβ T cells, they can be sorted into naive (CD27{sup +}CD45RA{sup +}), central memory (CD27{sup +}CD45RA{sup −}), effector memory (CD27{sup −}CD45RA{sup −}), and terminally-differentiated effector memory (CD27{sup −}CD45RA{sup +}) phenotypes. Here, we found that CD27{sup −}CD45RA{sup +} γδ T cells can be further divided into two populations based on the level of expression of CD45RA: CD27{sup −}CD45RA{sup int} and CD27{sup −}CD45RA{sup hi}. Those with the CD27{sup −}CD45RA{sup hi} phenotype lack extensive proliferative capacity, while those with the CD27{sup −}CD45RA{sup int} phenotype can be easily expanded by culture with zoledronate and IL-2. These CD27{sup -}CD45RA{sup hi} potentially exhausted γδ T cells were found predominantly in cancer patients but also in healthy subjects. We conclude that γδ T cells can be divided into at least 5 subsets enabling discrimination of γδ T cells with poor proliferative capacity. It was one of our goals to predict the feasibility of γδ T cell expansion to sufficient amounts for adoptive immunotherapy without the necessity for conducting small-scale culture tests. Fulfilling the ≥1.5% criterion for γδ T cells with phenotypes other than CD27{sup −}CD45RA{sup hi}, may help avoid small-scale culture testing and shorten the preparation period for adoptive γδ T cells by 10 days, which may be beneficial for patients with advanced cancer. - Highlights: • CD27{sup -}CD45{sup +} γδ T cells can be divided into two populations, CD27{sup -}CD45{sup hi} and CD27{sup -}CD45{sup int}. • CD27{sup -}CD45{sup hi} γδ T cells are detected in the peripheral blood of both cancer patients and healthy subjects. • CD27{sup -}CD45{sup hi} γδ T cells are distinct from so-called terminally differentiated CD27{sup -}CD45{sup int} γδ T cells. • CD27{sup -}CD45{sup hi} γδ T cells lack vigorous proliferative potential.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway

Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p. Overexpression of PRRT2 strongly impaired the cell viability and promoted cell apoptosis and these anti-tumor effects could be largely reversed by microRNA-30a-5p. Mechanistically, PRRT2 expression was closely correlated genes involved in unfolded protein response (UPR) pathway and introduction of PRRT2 inhibited gene expression in the three branches of UPR, including PERK axis, IRE1 axis and ATF6 axis. Taken together, our findings identify PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention. - Highlights: • PRRT2 is decreased in glioma and is targeted by miR-30a-5p. • PRRT2 exhibits tumor-suppressive effects on glioma cells. • PRRT2 correlates genes involved in unfolded protein response. • Over-expressed PRRT2 induces unfolded protein response in glioma in vitro.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

CNPY2 promoted the proliferation of renal cell carcinoma cells and increased the expression of TP53

Renal cell carcinoma (RCC) is the most common type of kidney cancer. However, the mechanisms underlying the progression of the disease are not well understood. The data in this report suggest that canopy FGF signaling regulator 2 (CNPY2) is a promoter of RCC progression. We found that CNPY2 significantly promoted growth of RCC cells and upregulated TP53 gene expression. Although TP53 is widely known as a tumor suppressor, in RCC TP53 promoted tumor cell growth. A typical p53 target gene, CDKN1A, was upregulated by both p53 and CNPY2 in RCC cells, suggesting that CNPY2 increased the expression level of TP53. Consistent with these results, CNPY2 and TP53 expression levels were positively correlated in RCC patients. These findings suggested that CNPY2 promoted cancer cell growth in RCC through regulating TP53 gene expression. - Highlights: • CNPY2 promoted growth of renal cell carcinoma (RCC) cells. • TP53 expression levels were increased by CNPY2 in RCC cells. • Growth of RCC cells was promoted by TP53. • CNPY2 expression positively correlated with TP53 expression in RCC patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Catalpol suppresses osteosarcoma cell proliferation through blocking epithelial-mesenchymal transition (EMT) and inducing apoptosis

Highlights: • Catalpol inhibits cell viability and EMT in osteosarcoma cell lines. • Catalpol induces apoptosis in osteosarcoma cell lines by Bcl-2/Caspase-8 signaling. • Catalpol induces ROS generation and suppresses STAT3 pathway activation. • Catalpol is able to suppresses osteosarcoma growth in vivo. Catalpol, an iridoid glucoside compound, is reported to possess diverse pharmacological actions. However, its effects on osteosarcoma are little to be known. In the present study, we showed that catalpol could strongly suppress osteosarcoma progression. Catalpol dose-dependently reduced the cancer cell viability. The migration of osteosarcoma cells was also consistently suppressed by catalpol treatment using the wound healing and transwell migration analysis. Catalpol reduced the expressions of Kras, receptor for activated C-kinase 1(RACK1) and matrix metalloproteinase (MMP)-2 in a dose-dependent manner, revealing the blockage of migration. Moreover, both intrinsic and extrinsic apoptosis were triggered by catalpol, as evidenced by improved cleaved Caspase-8/-9/-3 and Poly-(ADP-ribose) polymerase (PARP). Release of Cyto-c in cytoplasm and Bax up-regulation in total cells were observed in catalpol-treated cells, while mitochondrial Cyto-c and cellular Bcl-2 were down-regulated by catalpol. Reactive oxygen species (ROS) production was also involved in catalpol-induced cell death. Further, ROS scavenger, N-acetylcysteine (NAC), impeded catalpol-caused apoptosis. And suppression of signal transducer and activator of transcription 3/Janus kinase 2 gene/Src (STAT3/JAK2/Src) was involved in catalpol-induced cell death. In vivo, catalpol showed effective ability to reduce the tumor growth. Our results illustrated that catalpol might be considered as a promising pharmacological agent to suppress osteosarcoma.

60 APPLIED LIFE SCIENCES↗